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Inhibition of cAMP-dependent protein kinase A: a novel cyclo-oxygenase-independent effect of non-steroidal anti-inflammatory drugs in adipocytes

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Abstract:

Summary

1 Non-steroidal anti-inflammatory drugs (NSAIDs) [acetylsalicylic acid (ASS), naproxen, nimesulide and piroxicam] decreased adrenaline- or dibutyryl cAMP-stimulated glycerol release in isolated adipocytes. We aimed to determine the mechanism of this NSAIDs action.

2 Non-steroidal anti-inflammatory drugs decreased cAMP-dependent protein kinase A (PKA) activity in rat adipocyte lysates and in a commercial bovine heart PKA holoenzyme. If added before cAMP, NSAIDs impaired PKA activation by the cyclic nucleotide; however, if PKA was first activated by cAMP, NSAIDs were ineffective. NSAIDs were also ineffective against PKA catalytic subunits.

3 Consequently, NSAIDs lowered hormone-sensitive lipase translocation from cytosol to lipid storage droplets in adipocytes lysates, the critical event to promote lipolysis.

4 These results indicate that inhibition of PKA activation explains NSAIDs-induced decrease in adrenaline-stimulated lipolysis. We suggest that reproduction of such inhibition in nociceptive cells might enhance the understanding of the mechanism underlying the analgesic effects of NSAIDs.

Keywords: adipocytes protein kinase A; cAMP-dependent protein kinase A activation; heart protein kinase A; non-steroidal anti-inflammatory drugs

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1474-8673.2007.00392.x

Affiliations: 1: Departamento de Bioquímica, Facultad de Medicina 2: Unidad de Biomedicina, Facultad de Estudios Superiores-Iztacala, Universidad Nacional Autónoma de México, México, D.F., México

Publication date: April 1, 2007

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